Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner

BackgroundThe mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis.MethodsWe recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight ((wa)FAV).ResultsAt ultrasound 1, (wa)FAV was smaller in high versus low ACE males (b = - 0.17; z = - 3.75; p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72; p = .086). Compared to low ACE males, (wa)FAV was smaller for low (b = - 0.20; z = - 4.10; p < .001) and high ACE females (b = - 0.11; z = 2.16; p = .031); however, high ACE males did not differ from low (b = 0.03; z = .57; p = .570) or high ACE females (b = - 0.06; z = - 1.29; p = .196). At ultrasound 2, (wa)FAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps >= .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps >= .148).ConclusionsWe observed a significant impact of high maternal ACE history on (wa)FAV, a proxy for fetal adrenal development, but only in males. Our observation that the (wa)FAV in males of mothers with a high ACE history did not differ from the (wa)FAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes.

Automated summary

This study found that high maternal adverse childhood experiences (ACE) were associated with fetal adrenal development, but only in males. This observation extends preclinical research and suggests that gestational stress may have dysmasculinizing effects on offspring outcomes.